(a) Field of the Invention
This invention relates to 5-(phenyl)-1,6-naphthyridin-2(1H)-ones, their cardiotonic use and their preparation.
(b) Information Disclosure Statement
Hawes et al., J. Heterocyclic. Chem. 11 (2), 151-155 (1974), show the preparation of 3-phenyl-1,6-naphthridin-2(1H)-one and 3-(4-nitrophenyl)-1,6-naphthyridin-2(1H)-one by reacting 4-aminonicotinaldehyde with ethyl phenylacetate and ethyl 4-nitrophenylacetate, respectively. No utility is shown for either compound.
Lesher and Singh in U.S. Pat. No. 4,415,580, issued Nov. 15, 1983, shows as cardiotonic agents 5-(lower-alkyl)-1,6-naphthyridin-2(1H)-ones (I) and their preparation by reacting a 5-(lower-alkanoyl)-6-methyl-2(1H)-pyridinone with di-(lower-alkyl)formamide di-(lower-alkyl)acetal to produce 5-(lower-alkanoyl)-6-[2-(di-lower-alkylamino)ethenyl]-2(1H)-pyridinone (II) and reacting II with formamidine or ammonia or salt thereof to produce I.
Lesher and Singh in U.S. Pat. No. 4,412,077, issued Oct. 25, 1983, show as cardiotonic agents 5-(lower-alkanoyl)-6-(lower-alkyl)-2(1H)-pyridinones (I) and their preparation by reacting 2-(lower-alkanoyl)-1-(lower-alkyl)-ethenamine (II) with a lower-alkyl 2-propynoate.
Kato et al. [J. Heterocyclic Chem. 18, 603-606 (1981)] show, inter alia, the dehydrogenation of 5-acetyl-3,4-dihydro-6-methyl-2(1H)-pyridinone by heating it with palladium black to produce 5-acetyl-6-methyl-2(1H)-pyridinone, which in turn is reacted with phosphorus oxychloride (phosphoryl chloride) to produce a mixture of 6-chloro-3-ethynyl-2-methylpyridine and 6-chloro-3-(1-chlorovinyl)-2-methylpyridine.
Kato et al. [Chem. Pharm. Bull. 17, 2411-2416 (1969)] disclose the preparation of 5-acetyl-3,4-dihydro-6-methyl-2(1H)-pyridinone in two ways: (a) by refluxing 4-oxo-2-penten-2-amine and acrylic anhydride in chloroform (75% yield); and (b) by heating 4-oxo-2-penten-2-amine and ethyl acrylate in ethanol containing sodium ethoxide (9% yield).